@article{LodhaMuchsinJuergesetal.2023,
  author    = {Lodha, Manivel and Muchsin, Ihsan and J{\"u}rges, Christopher and Juranic Lisnic, Vanda and L'Hernault, Anne and Rutkowski, Andrzej J. and Prusty, Bhupesh K. and Grothey, Arnhild and Milic, Andrea and Hennig, Thomas and Jonjic, Stipan and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars},
  title     = {Decoding murine cytomegalovirus},
  series = {PLOS Pathogens},
  volume    = {19},
  journal   = {PLOS Pathogens},
  number    = {5},
  issn      = {1553-7374},
  doi       = {10.1371/journal.ppat.1010992},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350480},
  year      = {2023},
  abstract  = {The genomes of both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) were first sequenced over 20 years ago. Similar to HCMV, the MCMV genome had initially been proposed to harbor ≈170 open reading frames (ORFs). More recently, omics approaches revealed HCMV gene expression to be substantially more complex comprising several hundred viral ORFs. Here, we provide a state-of-the art reannotation of lytic MCMV gene expression based on integrative analysis of a large set of omics data. Our data reveal 365 viral transcription start sites (TiSS) that give rise to 380 and 454 viral transcripts and ORFs, respectively. The latter include 200 small ORFs, some of which represented the most highly expressed viral gene products. By combining TiSS profiling with metabolic RNA labelling and chemical nucleotide conversion sequencing (dSLAM-seq), we provide a detailed picture of the expression kinetics of viral transcription. This not only resulted in the identification of a novel MCMV immediate early transcript encoding the m166.5 ORF, which we termed ie4, but also revealed a group of well-expressed viral transcripts that are induced later than canonical true late genes and contain an initiator element (Inr) but no TATA- or TATT-box in their core promoters. We show that viral upstream ORFs (uORFs) tune gene expression of longer viral ORFs expressed in cis at translational level. Finally, we identify a truncated isoform of the viral NK-cell immune evasin m145 arising from a viral TiSS downstream of the canonical m145 mRNA. Despite being ≈5-fold more abundantly expressed than the canonical m145 protein it was not required for downregulating the NK cell ligand, MULT-I. In summary, our work will pave the way for future mechanistic studies on previously unknown cytomegalovirus gene products in an important virus animal model.},
  language  = {en}
}
@article{StaudtZieglerMartinVisekrunaetal.2023,
  author    = {Staudt, Sarah and Ziegler-Martin, Kai and Visekruna, Alexander and Slingerland, John and Shouval, Roni and Hudecek, Michael and Van den Brink, Marcel and Luu, Maik},
  title     = {Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy},
  series = {Frontiers in Immunology},
  volume    = {14},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2023.1269015},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328019},
  year      = {2023},
  abstract  = {The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies using chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. The great success in the context of hematologic malignancies has made especially CAR T cell therapy a promising approach capable of achieving long-lasting remission. However, the causalities involved in mediating resistance to treatment or relapse are still barely investigated. Research on T cell exhaustion and dysfunction has drawn attention to host-derived factors that define both the immune and tumor microenvironment (TME) crucially influencing efficacy and toxicity of cellular immunotherapy. The microbiome, as one of the most complex host factors, has become a central topic of investigations due to its ability to impact on health and disease. Recent findings support the hypothesis that commensal bacteria and particularly microbiota-derived metabolites educate and modulate host immunity and TME, thereby contributing to the response to cancer immunotherapy. Hence, the composition of microbial strains as well as their soluble messengers are considered to have predictive value regarding CAR T cell efficacy and toxicity. The diversity of mechanisms underlying both beneficial and detrimental effects of microbiota comprise various epigenetic, metabolic and signaling-related pathways that have the potential to be exploited for the improvement of CAR T cell function. In this review, we will discuss the recent findings in the field of microbiome-cancer interaction, especially with respect to new trajectories that commensal factors can offer to advance cellular immunotherapy.},
  language  = {en}
}